Resources
Authors & Affiliations
János Konkoly, Viktória Kormos, Balázs Gaszner, Dóra Zelena, Erika Pintér
Abstract
Introduction: Transient receptor potential ankyrin 1 (TRPA1) is a non-selective cation channel expressed in the urocortin 1 (UCN1) positive neurons of the centrally projecting Edinger-Westphal nucleus (EWcp) having modulatory impact on stress adaptation. As post-traumatic stress disorder (PTSD) is triggered by disturbed stress adaptation, we hypothesized the regulatory role of EWcp/UCN1/Trpa1 neurons in PTSD.Methods: Male TRPA1 wild-type (WT) and knockout (KO) mice were exposed to two different models of PTSD. In single prolonged stress (SPS) paradigm, time spent immobility was measured during forced swim test (FST) indicating depression-like behaviour. Upon foot-shocks model, jumping frequency was assessed as characteristic parameter for hyperarousal. Trpa1 and Ucn1 mRNA expressions as well as UCN1 peptide contents were measured in the EWcp/UCN1 neurons applying RNAscope technique combined with immunofluorescence.Results: Enhanced immobility combined with increased UCN1 peptide content was detected in stressed WT animals upon SPS, while similar changes were not detectable in KO mice. The basal Ucn1 mRNA expression was higher in KOs, however its level was not altered in any SPS-exposed groups. Using foot-shock, elevated stress-induced jumping rate was detected in KO animals, while shock-induced enhancement of Ucn1 mRNA level was observed only in WT animals associated with similarly changing tendencies of UCN1 peptide content. Trpa1 mRNA was downregulated in stressed groups of both models.Conclusion: Reduced Trpa1 mRNA expression in WT animals and unaltered UCN1 turnover in KO mice along with the increased hypervigilance and absence of depression-like behaviour may suggest the role of TRPA1 in the development of PTSD symptoms.